In a virus of the family Herpesviridae, a core protein is surrounded by double-stranded DNA with molecular masses of 80-150×106 Daltons which is enclosed in an icosahedral capsid with a diameter of about 100 nm which consists of 162 capsomers to form a nucleocapsid which is surrounded by an envelope to have an overall size of ca. 150-200 nm. Herpes viruses have been found in almost all mammals and amphibians and, in particular, viruses of the family Herpesviridae which have host specificity for humans are named human herpesviruses (HHVs). HHVs are classified into subfamilies alpha-herpesvirinae (e.g., herpes simplex virus and varicella zoster herpes virus), beta-herpesvirinae (e.g., cytomegalovirus), and gamma-herpesvirinae (e.g., EB virus).
Such herpes viruses are characterized by “latent infection”. The “latent infection” refers to an infection state in which viruses exist without production of infectious virus particles in host cells. In the latent infection, the virus gene and the gene product assisting the existence of the virus gene are retained in the host cells. It is known that herpes viruses under the latent infection are reactivated by any factor of the host, for example, increasing age or deconditioning (e.g. fatigue), so that a large number of viruses are duplicated through restart of production of virus particles (reactivation).
Accordingly, herpes viruses have unique properties; although they continue latent infection as long as the host is normal, they are reactivated to seek any other host if they scent the crisis of the host due to disturbance in the body of the host.
Comprehension on the latent infection and reactivation of viruses are essential for investigation of ecology of viruses of the family Herpesviridae. Unfortunately, sufficient knowledge is given to only the EB virus of the family gamma-herpesvirinae among the herpes viruses, and other viruses remains still unclear.
In particular, no additional information other than knowledge which was previously presented by some of the present inventors is disclosed on factors of beta-herpes viruses which involve latent infection. For example, Non-Patent Literature 1 discloses HHV-6 which is in a state of latent infection in macrophages exhibiting relatively high differentiation in peripheral blood, and also discloses the site of the latent infection with HHV-6 in the host. Non-Patent Literature 2 discloses high-rate transfer of HHV-6 into brain at the initial infection, which causes persistent infection or latent infection. Non-Patent Literature 3 discloses a gene expressed by the latent infection with HHV-6 (latent infection gene) and suggests that the gene controls the latent infection and reactivation of the viruses.
Non-Patent literature 4 shows that the state of latent infection with HHV-6 involves an intermediate stage which is comparatively stable and allows for active gene expression, with a result that a latent infection gene and a protein encoded by this gene (the latent infection gene protein) are expressed abundantly. Furthermore, Non-Patent Literature 5 shows that patients with chronic fatigue syndrome have in their serum antibodies against latent infection gene proteins the expression of which is enhanced at the intermediate stage.